1. Field of the Invention
The invention generally relates to methods of using hepatocyte growth factor (HGF) mimics to treat dementia and Parkinson's disease.
2. Background of the Invention
Dementia
There are approximately 10 million diagnosed dementia patients in the United States alone and that number continues to grow every year as the population ages. The costs of treatment and care of these patients are in excess of $70 billion annually and are increasing rapidly. Unfortunately, the current treatment options for the management of dementia are severely limited and largely ineffective. The lack of treatment options for a burgeoning health problem of this magnitude necessitates that new and innovative therapeutic approaches be developed as quickly as possible.
At its core dementia results from a combination of diminished synaptic connectivity among neurons and neuronal death in the entorhinal cortex, hippocampus and neocortex. Therefore, an effective treatment would be expected to augment synaptic connectivity, protect neurons from underlying death inducers, and stimulate the replacement of lost neurons from preexisting pools of neural stem cells. These clinical endpoints advocate for the therapeutic use of neurotrophic factors, which mediate neural development, neurogenesis, neuroprotection, and synaptogenesis. Neurotrophic factors have been considered as treatment options for many neurodegenerative diseases including Alzheimer's disease.
Parkinson's Disease
A treatment option long considered for Parkinson's disease (PD) has been the application of growth factors with the intention of halting disease progression, restoring lost function, or hopefully both. However, this dream has gone largely unfulfilled at the level of clinical medicine because of limitations related to brain delivery and costs. Growth factors are universally large proteins that are both metabolically labile and too large to pass the blood-brain barrier (BBB). As such, most approaches to delivery have utilized gene therapy methods with the hope that the growth factor will be expressed in the correct location at a high enough concentration and for a long enough period to provide clinical relief. Although a number of creative and successful approaches in animal models have been employed to deliver growth factors (e.g. GDNF) to the brain, these methodologies are technically complex and prohibitively difficult to bring to practice with large numbers of patients.
Unfortunately, the direct use protein neurotrophic factors as therapeutic agents has at least two serious limitations: 1) their large size and hydrophilic character preclude blood-brain barrier permeability (BBB); and 2) the need to manufacture such proteins by recombinant methods at high cost would limit their widespread use.
It would be a boon to have available molecules with growth factor activity which are orally active, display profound growth factor activity, and yet are inexpensive to synthesize, for the treatment of dementia and PD.